SPID#: 60 Growth hormone (GH) and its primary effector, insulin-like growth factor- I (IGF-I), govern the tempo and degree of adolescent growth. In addition to anabolic effects, the GH axis may regulate the hypothalamic-pituitary - ovarian unit (HPO) during puberty and affect ovarian physiology in adults. It is not clear whether the GH axis is obligatory for the normal progression of puberty and adult fertility and, if so, whether these effects are mediated through changes in H-P regulation of luteinizing hormone releasing hormone and LH and/or ovarian sensitivity. Studies were initiated this year, using female rhesus monkeys, that will not only clarify the neuroendocrine regulation of the GH axis in adolescents and adults but will also determine whether the effects of GH and IGF-I on reproduction are limited to the puberty and how these may alter the HPO function, regulating LH secretion. Age-dependent changes in pulsatile GH secretion are being assessed in intact (n = 12) and ovariectomized (OVX; n= 12) adolescent females and OVX adult females (n = 10) treated with varying doses of estradiol (E2) to determine if the regulation of pulsatile GH by E2 is differentially affected by age. In addition, one half of the animals in each group are being treated with IGF-I (100 5g/kg/day, SC) to determine if IGF-I differentially regulates pulsatile GH under specific E2 treatment conditions and E2 negative feedback of LH in adult and adolescent females. The response in GH secretion is being assessed at specific ages following administration of GH releasing hormone (hGHRH-40). In addition, the response in GH and LH secretion under varying treatment conditions is being assessed following treatment with the excitatory amino acid, NMDA. Basal serum samples are also being collected twice weekly and are being assayed for IGF-I, IGFBP-3, GHBP, E2, LH, and progesterone (gonadally intact groups only). The results of these studies will significantly advance our understanding of how GH synthesis and secretion is regulated in adolescent and adult females. Since GH is an important metabolic and anabolic hormone, a more clear understanding of how GH is released from adolescence through adulthood may provide insights into treatment methods for abnormalities in the GH axis. In addition, these data will also determine the importance of GH and IGF-I in controlling reproduction in females and whether the positive effects of these growth factors on fertility act at the level of the brain or the gonad. This information may assist in the clinical treatment of infertility.
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